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PubMed1990

[Regulation of secretion and synthesis of gastrointestinal hormones: studies with cultured gut endocrine cells].

Small number of endocrine cells are diffusely distributed in the gut mucosa. Studies on their secretory mechanisms have been further complicated by numerous neural, paracrine, and endocrine factors affecting their response. Recent technical development for isolation and culture of gut endocrine cells has circumvented these problems and enabled to study their receptors, signal transduction mechanism, and biosynthesis of gut hormones. In this review, current progress made in the cellular physiology of gut endocrine cells is summarized.

Animals↗
PubMed1986

Circulating gastrointestinal hormones in patients with flatulent dyspepsia, with and without gallbladder disease.

Fasting and post-prandial circulating levels of insulin, gastrin, gastric inhibitory polypeptide, pancreatic polypeptide and neurotensin were measured in patients with flatulent dyspepsia, with and without gallbladder disease and post-cholecystectomy. Levels were also measured in non-dyspeptic patients with gallbladder disease and normal controls. There were no consistent significant differences from controls for fasting and post-prandial responses in patients with a history of dyspepsia or those who experienced dyspepsia at the time of the test. In patients with gallbladder disease, with and without dyspepsia, there was a reduced neurotensin response compared to normal controls. It is concluded that circulating levels of these hormones are not related to symptoms of flatulent dyspepsia.

Dyspepsia↗
PubMed1979

Gastrointestinal hormones in clinical disease: recent developments.

With the advent of radioimmunoassay and immunocytochemical methods, the peptides of the gastrointestinal tract have been identified and measured. Gastrinoma and insulinoma syndromes have been wall characterized. The pancreatic cholera syndrome and some of the evidence that the major manifestations of this disease may be mediated by vasoactive intestinal peptide have been re-examined. Pancreatic polypeptide seems to be an ideal peptide for study of vagal-cholinergic mechanisms that regulate hormone release; it also appears to be a tumor marker for several types of pancreatic endocrine tumors, particularly those of pancreatic cholera. Secretin and cholecystokinin are important regulators of pancreatic exocrine secretion and have been used to test pancreatic function, but there is little evidence that they account for clinical disease. Glucagon-secreting tumors produce a clinical syndrome of diabetes mellitus and distinctive skin lesions, which can be cured by tumor resection. Hormone-secreting tumors may provide insight into normal gut physiology.

Adenoma, Islet Cell↗
PubMed1986

Gastrointestinal hormones in alcoholic patients with and without liver disease.

To assess the effects of both alcoholism and liver disease on gastroentero-pancreatic hormones, fasting and post-prandial concentrations were analysed in the following four groups: (1) Alcoholic subjects with liver disease; (2) Alcoholic subjects without liver disease; (3) Control subjects with liver disease; (4) Control subjects without liver disease.Liver disease was associated with increased fasting serum glucose, plasma insulin, pancreatic polypeptide, gastrin and vasoactive intestinal polypeptide. Alcoholism in the absence of liver disease did not influence either the fasting or post-prandial concentrations of serum glucose, plasma gastrin, insulin, pancreatic polypeptide, gastric inhibitory polypeptide, N- and C-terminal glucagon or vasoactive intestinal polypeptide. Alcoholism with liver disease depressed plasma gastric inhibitory polypeptide concentrations. The results suggest that the abnormalities in gastroenteropancreatic hormone in alcoholics are likely to be related to liver disease which is often concurrent.

Adult↗
PubMed1980

The effect of pirenzepine on meal-stimulated gastrointestinal hormones.

The effects of pirenzepine on the plasma concentrations of gut hormones in the fasting and postprandial states were studied in six healthy subjects. On separate days and in random order, 10 mg pirenzepine, in 2 ml of solvent, or 2 ml saline (0.15 mol/l) were given intravenously 30 min before a standard normal breakfast (2220 kJ). Pirenzepine was not found to affect basal or postprandial levels of insulin, glucagon, gastric inhibitory peptide (GIP), neurotensin, vasoactive intestinal peptide (VIP) or somatostatin. The basal concentration of pancreatic polypeptide (PP) was lowered (p less than 0.05) and the postprandial elevation reduced, though not significantly. While the basal concentration of motilin was also suppressed (p less than 0.05), the postprandial elevation remained unchanged following pirenzepine. The release of enteroglucagon was reduced significantly in the basal and postprandial states (p less than 0.05 and p less than 0.025 respectively). The postprandial gastrin response was prolonged slightly, but insignificantly, by pirenzepine. It is concluded that pirenzepine does not exert any major or unexpected actions on the hormonal control of digestion.

Adult↗
PubMed1987

The immediate effect of human renal transplantation on basal and meal-stimulated levels of gastrointestinal hormones.

Elevated serum levels of gastrin, pancreatic polypeptide, and glucagon were found in 10 uraemic patients, whereas gastric inhibitory polypeptide and somatostatin levels were normal. After renal transplantation there was a significant reduction in serum gastrin (median, 5 pmol/l; p = 0.05, n = 9), pancreatic polypeptide (145 pmol/l; p less than 0.01, n = 9), GIP (9.5 pmol/l; p = 0.02, n = 7), and glucagon (92 pg/l; p less than 0.02, n = 9), whereas no alteration was seen in the somatostatin level. Meal stimulation produced consistent increases in serum levels of all hormones, and the response appeared to be unchanged after renal transplantation.

Adult↗
PubMed1984

Effects of gastrointestinal hormones on ileal vascular and visceral smooth muscle.

Blood levels of gastrin, secretin, gastric inhibitory polypeptide (GIP), and cholecystokinin octapeptide (CCK-8) increase after a meal and may affect vascular and/or visceral smooth muscle. To study this possibility, we measured the effects of local intra-arterial infusion of these hormones on ileal perfusion pressure and intestinal wall compliance. In pentobarbital sodium-anesthetized dogs, a segment of ileum was exteriorized and vascularly perfused at constant flow with arterial blood. Wall compliance was calculated from the pressure generated by incremental changes in intraluminal volume (delta V/delta P). Postprandial blood levels of these hormones did not affect ileal perfusion pressure. However, higher blood levels of secretin and GIP did significantly lower perfusion pressure. Wall compliance was significantly increased by postprandial blood levels of secretin and GIP, while postprandial blood levels of CCK-8 decreased compliance. Gastrin was without effect on compliance. These data suggest these hormones do not contribute to postprandial ileal hyperemia. However, secretin, GIP, and CCK-8 do affect the postprandial activity of ileal visceral smooth muscle.

Animals↗
PubMed1990

Short-term effects of diethylaminoethyl-dextran on postprandial gastrointestinal hormone responses in man.

The effects of oral diethylaminoethyl-dextran (3 g total), taken 30 min before a standard mixed test meal, on plasma glucose, total cholesterol, triglycerides, total lipids, gastrin-like immunoreactivity, bombesin-like immunoreactivity, gastric-inhibitory-polypeptide-like immunoreactivity and neurotensin-like immunoreactivity were evaluated in eight healthy volunteers following a double-blind protocol. Incremental peak plasma concentrations of total lipids and triglycerides were significantly reduced by pretreatment with diethylaminoethyl-dextran pretreatment, while peaks of plasma glucose and total cholesterol were not significantly affected. Diethylaminoethyl-dextran also inhibited postprandial gastrin-like gastric-inhibitory-polypeptide-like and neurotensin-like immunoreactivity; by contrast, bombesin-like immunoreactivity was not significantly modified. The present study indicates that diethylaminoethyl-dextran is able to regulate some postprandial metabolic and hormonal parameters in man; consequently it might be useful in the treatment of hyperlipoproteinaemia and obesity.

Adult↗
PubMed1979

Some contributions to the chemistry of the gastrointestinal hormones.

Twenty-five years ago we described an extraction procedure for porcine secretin in which the intestinal tissue is briefly boiled in water and then extracted with dilute acid at low temperature. Boiling in water, which inactivates proteolytic enzymes, does not extract secretin, and extraction with acid in the cold will minimize cleavage of acid labile peptide structures. This extraction procedure has formed the basis for the isolation not only of secretin but also of cholecystokinin-pancreozymin (CCK) and, in collaboration with other laboratories, of the vasoactive intestinal peptide (VIP), the gastric inhibitory peptide (GIP), and motilin. Recently it has been used for the isolation of an N-terminally extended somatostatin from intestinal tissue, and of a peptide, from both nonantral gastric and intestinal tissues, with gastrin-releasing and probably cholecystokinin-releasing properties. A technique has been worked out permitting the chemical analysis, in certain cases, of polypeptide hormones in the presence of other polypeptides, the polypeptide mixture being exposed to fragmentation conditions known to result in characteristic hormone fragments, which are then extracted and quantitated. The technique can also be useful for the isolation of previously unknown peptides by identifying fragments of such and tracing them back to their peptides of origin.

Amino Acid Sequence↗
PubMed1982

Gastrointestinal hormones: central nervous system localization and sites of neuroendocrine actions.

It was established that VIP (vasoactive intestinal peptide), secretin, CCK (cholecystokinin), gastrin and motilin can be localized to the CNS by immunologic means. Whether or not these immuno-crossreactivities represent peptides identical to those in the g.i. tracts remains to be established. The neuronal localization of these five peptides in the gut predicted, however, their presence in neurons of the CNS. Furthermore, their presence within the hypothalamus and pituitary suggested physiological roles for these hormones in anterior pituitary function. We have now demonstrated the direct actions of VIP, secretin, gastrin and motilin on pituitary hormone release in vitro. Perhaps more importantly, we have described a hypothalamic site of action of VIP, secretin, CCK and gastrin to alter hormone release in vitro. Our data, taken in concert with those of other groups, suggest a modulatory role for the g.i. hormones and indicate the possible symphonic control by many hormones and transmitter candidates of distinct secretory events in the pituitary. Indeed, these data indicate the complexity underlying the finally tuned hypothalamus-pituitary-target tissue axis.

Animals↗
PubMed1978

Elevations of gastrointestinal hormones in chronic renal failure.

Fasting levels of 5 gut hormones were studied in 30 patients with advanced uraemia (CRF), 40 undergoing regular dialysis (RD) and 555 renal transplant patients (RT). Mean values of gastrin and total glucagon were markedly elevated in CRF and RD patients compared with 20 normal subjects; there were lesser elevations in pancreatic glucagon, insulin and vasoactive intestinal peptide (VIP). Secretin levels were unchanged. In RT patients, fasting levels of VIP and pancreatic glucagon had returned to normal, while levels of gastrin, total glucagon and insulin remained slightly elevated compared with controls. Food stimulated hormone levels were measured in 18 RD patients and compared with 18 controls. After eating, RD patients failed to show the late increase in total glucagon, or the suppression of VIP and secretin seen in normal subjects; the pattern of gastrin and insulin response was similar to controls, but after the initial increase plasma levels in RD patients tended to show a slower decline. Thus involvement of the gastrointestinal tract in uraemia is associated with functional disturbance of the endocrine system of the gut.

Gastrins↗
PubMed1991

Natural killer cell activity in patients with neuroendocrine tumours of the gastrointestinal tract; relation with circulating gastrointestinal hormones.

We have evaluated the peripheral blood natural killer (NK) cell activity and the in vitro effect of recombinant gamma-interferon (r gamma-IFN) on NK cell activity in 23 patients with a neuroendocrine tumour of the pancreas, small intestine or liver, and 23 healthy controls. Patients with a gastrinoma showed a NK cell activity which was not different from that of the control group, whereas patients with another type of neuroendocrine tumour had a decreased NK cell activity compared to the controls (p less than 0.05) and the gastrinoma patients (p less than 0.02). The impaired NK cell activity in these patients was as such not related to the presence of liver metastasis or performance status of the patients. r gamma-IFN significantly stimulated the NK cell activity in patients and controls. However, the cytotoxic response of the patients with a hormone production other than gastrin remained lower than in the two other groups. Follow-up studies in 8 patients showed NK cell activities not to vary with stable disease, to decrease with progressive disease, and to increase with regression of disease. In conclusion, NK cell activity is suppressed in patients with neuroendocrine tumours that produce hormones other than gastrin. This impairment is not related to the presence of metastasis but seems to be related to the course of the disease.

Adult↗
PubMed1982

Gastrointestinal hormones in clinical medicine.

Information concerning GEP hormones has progressively advanced since the initial discovery of a GEP hormone, secretin, in 1902. Studies in this area flourished with the advent of radioimmunoassay, and have provided an understanding of the secretion, regulation, metabolic actions, and role in certain diseases of major GEP hormones. Measurement of GEP hormones has achieved importance in clinical medicine and allowed understanding of the pathophysiology of several clinical disorders. The decade to come should witness additional advances in this rapidly expanding field.

Chemical Phenomena↗